Chromatin Accessibility Landscape of Cutaneous T Cell Lymphoma and Dynamic Response to HDAC Inhibitors

Cancer Cell. 2017 Jul 10;32(1):27-41.e4. doi: 10.1016/j.ccell.2017.05.008. Epub 2017 Jun 15.

Abstract

Here, we define the landscape and dynamics of active regulatory DNA in cutaneous T cell lymphoma (CTCL) by ATAC-seq. Analysis of 111 human CTCL and control samples revealed extensive chromatin signatures that distinguished leukemic, host, and normal CD4+ T cells. We identify three dominant patterns of transcription factor (TF) activation that drive leukemia regulomes, as well as TF deactivations that alter host T cells in CTCL patients. Clinical response to histone deacetylase inhibitors (HDACi) is strongly associated with a concurrent gain in chromatin accessibility. HDACi causes distinct chromatin responses in leukemic and host CD4+ T cells, reprogramming host T cells toward normalcy. These results provide a foundational framework to study personal regulomes in human cancer and epigenetic therapy.

Keywords: CTCL; HDAC inhibitor; cancer epigenetics; response predictor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromatin / chemistry
  • Chromatin / drug effects*
  • Cluster Analysis
  • Epigenomics
  • Gene Expression Regulation, Neoplastic*
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Humans
  • Lymphoma, T-Cell, Cutaneous / drug therapy
  • Lymphoma, T-Cell, Cutaneous / genetics*
  • RNA, Messenger / metabolism

Substances

  • Chromatin
  • Histone Deacetylase Inhibitors
  • RNA, Messenger